Benign prostatic hyperplasia (BPH) is common in older men, with symptoms that impact quality of life, including interference with activities and perception of well being. BPH can be progressive, with risk of urinary retention, infections, bladder calculi and renal failure. Although many men with mild to moderate symptoms do well without intervention, bothersome symptoms and complications can progress in others, leading to medical therapy or surgery.
One of the complications of BPH is acute urinary retention, leading to catheterization. Acute urinary retention may be classified as either spontaneous or precipitated. Spontaneous acute urinary retention is often considered by patients to be the most serious outcome of BPH.
Spontaneous acute urinary retention is an episode of acute urinary retention that is due to BPH and is not tied to a precipitating event. The 5.alpha.-reductase inhibitor finasteride has been shown to be effective in treating BPH and in significantly reducing spontaneous acute urinary retention in patients with BPH. Andersen et al., Urology, 49(6), 839-845 (1997).
Precipitated acute urinary retention is an episode of acute urinary retention that is precipitated by at least one of the following factors: anesthesia or surgery within 72 hours; a precipitating medical event such as stroke or congestive heart failure; a medical condition such as prostatitis or urinary tract infection; or ingestion of medication or drugs known to precipitate retention, e.g., pseudoephedrine hydrochloride, cold medicine, pain medication such as narcotics or sedatives, or benadryl.
Until the present invention, nu medical therapy for BPH was known to decrease the risk of or prevent precipitated acute urinary retention.
The enzyme 5.alpha.-reductase catalyzes the reduction of testosterone (T) to the more potent androgen, 5.alpha.-dihydrotestosterone (dihydrotestosterone" or DHT), as shown below: ##STR1##
There are two isozymes of 5.alpha.-reductase in humans. One isozyme (type 1) predominates in the sebaceous glands of skin tissue. The other (type 2) predominates in the prostate.
Finasteride (17.beta.-(N-tert-butylcarbamoyl)-3-oxo-4-aza-5.alpha.-androst-1-en-3-one) , as shown below, is a potent inhibitor of the human type 2 enzyme. ##STR2## Under the tradename PROSCAR.RTM., finasteride is known to be useful in the treatment of hyperandrogenic conditions, see e.g., U.S. Pat. No. 4,760,071. Finasteride is currently prescribed for the treatment of benign prostatic hyperplasia (BPH), a condition affecting to some degree the majority of men over age 55.
Also known are compounds which are potent inhibitors of both 5.alpha.-reductase type 1 and type 2. These include the compound described in U.S. Pat. No. 5,565,467.